Project 9: Inter-module integration - plasticity and robustness in brain and behavior (Hofmann) (#51-55) We explored the molecular basis of neural and behavioral plasticity in the African cichlid fish Astatotilapia burtoni. The males make regular transitions between territorial ("macho") and non-territorial ("wimp") forms, and we used a combination of behavioral observation and microarray analysis to map the genetic modules responsible for these dramatic behavioral and physiological transitions. We made a cDNA microarray containing 18,000 features from an estimated 8,000 genes21 and made arrays, DMA sequences, and the associated database freely available (http://cichlid.biosci.utexas.edu/html/cichlid genomics.html). an effort that sparked an NHGRI-approved initiative to sequence four cichlid genomes. Whole-brain expression profiling in individuals of known social status led us to perform detailed analysis on small groups of cells microdissected from the preoptic area of the hypothalamus. Examining gene expression in territorial and non-territorial males and correlating it with behavioral and physiological markers showed that genes can be grouped into a small number of modules, clusters where gene expression is highly correlated, and that expression of the modules correlates strongly with phenotypic traits. The relationships between the modules are interesting and complex. For example, aggressive and sexual behavior drive expression in opposite directions, echoing a theme from classical ethology, but both types of changes are inhibited by the acute stress response. We focused on the role of somatostatin and showed that this ancient peptide has a role in regulating aggressive behavior22. The cichlid fish have speciated explosively, and many different traits have appeared independently in separate lineages. We correlated ecological, behavioral, and neuroanatomical data for a single closely related clade (the Ectodini) and reached the conclusion that selection can act independently and rapidly on different regions of the brain, a finding that has direct relevance for the recent evolution of the human brain23. Hans Hofmann, the PI was a Bauer Fellow and is now Assistant Professor of Integrative Biology at UT-Austin.